Orally administered corticosteroid compositions

Abstract

The present invention is directed to orally administered corticosteroid compositions. The present invention also provides a method for treating a condition associated with inflammation of the gastrointestinal tract in an individual. The method comprises administering to an individual in need thereof a pharmaceutical composition of the present invention.

What is claimed is: 
     
       1. An oral, liquid pharmaceutical composition comprising budesonide, a pharmaceutically acceptable liquid, and a phase change agent dissolved or suspended in the pharmaceutically acceptable liquid, wherein after oral administration to a patient, said composition undergoes a change in physical properties of the composition upon contact with the upper gastrointestinal tract of said patient, whereby contact of the corticosteroid with the upper gastrointestinal tract of the patient is enhanced and/or prolonged. 
     
     
       2. The liquid pharmaceutical composition of  claim 1 , wherein the budesonide is suspended in the pharmaceutically acceptable liquid. 
     
     
       3. The liquid pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable liquid is selected from the group consisting of water, pharmaceutically acceptable alcohols, oils, glycols, glycol ethers, pyrrolidones, polyethylene glycols, N-methyl-2-pyrrolidone, 2-pyrrolidone, glycerol, tetraglycol, glycerol formal, solketal, ethyl acetate, ethyl lactate, ethyl butyrate, dibutyl malonate, tributyl citrate, tri-n-hexyl acetylcitrate, diethyl succinate, diethyl glutarate, diethyl malonate, triethyl citrate, triacetin, tributyrin, diethyl carbonate, propylene carbonate, acetone, methyl ethyl ketone, dimethyl sulfoxide, dimethyl sulfone, tetrahydrofuran, caprolactam, N,N-diethyl-m-toluamide, 1-dodecylazacycloheptan-2-one, 1,3-dimethyl-3,4,5,6-tetrohydro-2(1H)-pyrimidinone, and combinations thereof. 
     
     
       4. The liquid pharmaceutical composition of  claim 1 , wherein the liquid composition is an aqueous suspension or solution. 
     
     
       5. The liquid pharmaceutical composition of  claim 1 , wherein after administration to a patient, said composition precipitates onto the mucosa of the gastrointestinal tract of the patient, whereby deposition of the corticosteroid onto the mucosa of the gastrointestinal tract is enhanced and/or prolonged. 
     
     
       6. The liquid pharmaceutical composition of  claim 1 , wherein after administration to a patient, said composition forms a gel on contact with the mucosa of the gastrointestinal tract of the patient, whereby the deposition of the corticosteroid onto the mucosa of the gastrointestinal tract is enhanced and/or prolonged. 
     
     
       7. The liquid pharmaceutical composition of  claim 1 , wherein after administration to a patient, said composition increases in viscosity upon contact with the mucosa of the gastrointestinal tract of the patient, whereby the residence time of the corticosteroid on the mucosa of the intestinal tract is prolonged. 
     
     
       8. The liquid pharmaceutical composition of  claim 1 , wherein said phase change agent is a poorly water-soluble polymer. 
     
     
       9. The liquid pharmaceutical composition of  claim 1 , wherein said phase change agent is a thermosensitive polymer whose aqueous viscosity changes in the range of about 15 to about 40° C. 
     
     
       10. The liquid pharmaceutical composition of  claim 1 , wherein said phase change agent increases in viscosity upon contact with fluids of the oropharynx. 
     
     
       11. The liquid pharmaceutical composition of  claim 1 , wherein said pharmaceutically acceptable liquid is water-miscible. 
     
     
       12. The liquid pharmaceutical composition of  claim 1 , wherein said phase change agent is a bio-gelling polymer selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polydioxannones, polycarbonates, polyhydroxybutyrates, polyalkyene oxalates, polyanhydrides, polyamides, polyesteramides, polyurethanes, polyacetals, polyketals, polyorthocarbonates, polyphosphazenes, polyhydroxyvalerates, polyalkylene succinates, poly(malic acid), poly(amino acids), chitin, chitosan, polyorthoesters, cellulose derivatives, cellulose esters, methacrylic acid and methacrylate polymers, and copolymers, terpolymers and mixtures thereof. 
     
     
       13. The liquid pharmaceutical composition of  claim 12 , wherein said bio-gelling polymer is ethylcellulose. 
     
     
       14. The liquid pharmaceutical composition of  claim 10 , wherein said increase in viscosity is at least 50%. 
     
     
       15. A method for treating an inflammatory condition of the upper gastrointestinal tract comprising orally administering to an individual in need thereof the oral, liquid pharmaceutical composition of  claim 1 . 
     
     
       16. The method of  claim 15 , wherein said inflammatory condition is eosinophilic esophagitis. 
     
     
       17. The method of  claim 15 , wherein said inflammatory condition comprises inflammation of the glottis, epiglottis, tonsils, oropharynx, or esophagus. 
     
     
       18. The method of  claim 15 , wherein said inflammatory condition is viral or bacterial pharyngitis. 
     
     
       19. The method of  claim 15 , wherein said inflammatory condition is gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD) or erosive esophagitis. 
     
     
       20. The method of  claim 15 , wherein the amount of budesonide administered is from about 0.01 mg to about 20 mg. 
     
     
       21. The method of  claim 15 , wherein the amount of budesonide administered is about 20 mg.